This project is aimed at natural products drug discovery; the purpose is to do exploratory research on the isolation, biological testing, and identification of potentially useful natural products from tropical rainforest plants of North Queensland, Australia. We are faced with ever-increasing health threats from "exotic" and opportunistic infections, multidrug resistant pathogens and cancers. In order to combat these important health problems, discovery of new medicinal agents with novel modes of activity is imperative. Higher plants can provide compounds with new structural features and novel mechanisms of biological activity. As prototype medicinal agents, they may provide starting points for synthetic or semisynthetic modifications aimed at enhancing their potency or therapeutic potential. The specter of emerging and reemerging infectious diseases spells out the need to identify new and complementary antimicrobial agents to combat these unusual pathogens and natural products are an obvious source. In this project, plant materials will be screened for antibacterial, antifungal, and antiviral activity. Cancer continues to be a major cause of death in the United States and the development of multidrug resistant tumors exacerbates the problem and necessitates the discovery of additional chemotherapeutic agents. Natural products represent a potential source of new antineoplastic agents with novel structure, composition, and mode of bioactivity. A second goal of our proposed research is, therefore, to screen natural products against a battery of tumor cell lines for in-vitro cytotoxic or cytostatic antitumor activity.. This project will involve collection of heretofore unstudied Australian tropical rainforest plants (especially those from the families Euphorbiaceae, Lauraceae, Mimosaceae, Myrtaceae, and Xanthophyllaceae) solvent extraction of these plants, and screening of the crude extracts for biological activity (anti-HSV, antimicrobial, and cytotoxic activity). Extracts which show promising activity will be separated, the active components isolated and purified using activity-directed chromatographic techniques, and the structures of the active compounds determined using spectroscopic and crystallographic methods. This research project provides the potential of discovering novel phytochemical materials as medicinal agents in our battle against human illnesses. An especially attractive feature of this project is the interdiscipiinwy nature of the research. There are three principal investigators and an additional three collaborators who bring many different areas of complementary expertise into the project. The collaboration with the Botany Department at James Cook University of North Queensland especially, brings a unique research opportunity and access to materials not generally available. In addition, the project provides excellent hands-on experience for undergraduate students not only from the University of Alabama in Huntsville, but also from James Cook University. These institutions are committed to undergraduate research participation as part of quality scientific education.